Potassium Phosphate, Tribasic → 5-Methoxy-N-(4-(7-methoxy-1,5-naphthyridin-4-yloxy)phenyl)pyridazin-3-amine

HRID 1042904Notes

Reaction equation

P([O-])([O-])([O-])=O.[K+].[K+].[K+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.[CH3:51][O:52][C:53]1[CH:62]=[C:61]2[C:56]([C:57]([O:63][C:64]3[CH:69]=[CH:68][C:67]([NH2:70])=[CH:66][CH:65]=3)=[CH:58][CH:59]=[N:60]2)=[N:55][CH:54]=1.Cl[C:72]1[N:73]=[N:74][CH:75]=[C:76]([O:78][CH3:79])[CH:77]=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[CH3:79][O:78][C:76]1[CH:77]=[C:72]([NH:70][C:67]2[CH:68]=[CH:69][C:64]([O:63][C:57]3[C:56]4[C:61](=[CH:62][C:53]([O:52][CH3:51])=[CH:54][N:55]=4)[N:60]=[CH:59][CH:58]=3)=[CH:65][CH:66]=2)[N:73]=[N:74][CH:75]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A pyrex reaction tube was charged with potassium phosphate (88 mg, 415 μmol), Pd2dba3 (16 mg, 17 mmol), Xantphos (22 mg, 38 mmol), 4-(7-methoxy-1,5-naphthyridin-4-yloxy)benzenamine (92 mg, 346 μmol), 3-chloro-5-methoxypyridazine (50 mg, 346 μmol), and toluene (1 mL). The tube was purged with argon, sealed, and the mixture was heated at 100° C. for 4 h. LCMS showed complete conversion to desired product. The mixture was then concentrated and purified by silica gel chromatography using 0 to 60% (90/10/1 DCM/MeOH/ammonium hydroxide) in DCM. MS: M+H+=376.

Workup

customThe tube was purged with argon
customsealed
concentrationThe mixture was then concentrated
custompurified by silica gel chromatography

Sources & evidence

ORD record: ord-0717bdd5c93c4302bf0104753c928938
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08557816B2

Reaction notes

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